title: Depurination of N7-methylguanine by DNA glycosylase AlkD is dependent on the DNA backbone.
abstract: DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown mechanism, in which the damaged nucleotide is positioned away from the protein and the phosphate backbone is distorted. Here, we show by methylphosphonate substitution that a phosphate proximal to the lesion has a significant effect on the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a conventional mechanism whereby protein side chains participate in N-glycosidic bond cleavage, AlkD remodels the DNA into an active site composed exclusively of DNA functional groups that provide the necessary chemistry to catalyze depurination.
authors.affiliation: Department of Biological Sciences, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Rubinson
authors.forename: Plamen P
authors.initials: PP
authors.lastname: Christov
authors.forename: Brandt F
authors.initials: BF
authors.lastname: Eichman
mesh_terms: D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D045647:DNA Glycosylases / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011687:Purines / Q000378:metabolism*
chemical_list: D011687:Purines; D006147:Guanine; C008450:7-methylguanine; D004247:DNA; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases